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Detection and identification ofPodophyllotoxin produced by cell cultures derived from podophyllum hexandrum royle

The phenylpropanoid derived lignan podophyllotoxin, occurring inPodophyllum species, is used as a starting compound for the chemical synthesis of the antitumour agents etoposide (VP-16-213) and teniposide (VM-26). At present, the availability of this lignan becomes increasingly limited. As an alternative source, cell cultures originating fromPodophyllum hexandrum Royle were initiated. Analysis of the cell extracts using different HPLC systems as well as TLC, indicated the presence of podophyllotoxin. After prepurification of the extracts by means of ITLC, the identity was confirmed by mass spectrometric analysis. Dark-grown cultures accumulated considerable higher amounts of podophyllotoxin in comparison with the light-grown cultures.     

Declining incidence of AIDS dementia complex after introduction of zidovudine treatment.

OBJECTIVE--To assess the incidence of the AIDS dementia complex and the presence of HIV I p24 antigen in cerebrospinal fluid in relation to zidovudine treatment. DESIGN--Retrospective study of a consecutive series of patients with AIDS from 1982 to 1988. SETTING--An academic centre for AIDS. PATIENTS--196 Patients with AIDS and neurological symptoms examined from 1982 to 1988. INTERVENTIONS--Zidovudine treatment, which was introduced to The Netherlands on 1 May 1987 for patients with severe symptoms of HIV infection (Centers for Disease Control groups IVA, B, C, and D). MAIN OUTCOME MEASURES--Diagnosis of AIDS dementia complex and presence of HIV I p24 antigen in cerebrospinal fluid. RESULTS--The AIDS dementia complex was diagnosed in 40 of the 196 (20%) patients with AIDS. Thirty eight of 107 patients with AIDS (36%) not taking zidovudine developed the AIDS dementia complex compared with two of the 89 (2%) taking the drug (p less than 0.00001). The incidence of the AIDS dementia complex increased to 53% in the first half of 1987, after the introduction of zidovudine in May 1987, decreasing to 10% in the second half of 1987 and to 3% in 1988. Dementia was diagnosed before definition of the AIDS dementia complex (1986) according to DSM-III criteria and there was good agreement between diagnosis before and after 1986. Sixteen of 61 samples of cerebrospinal fluid (26%) from patients with AIDS (10 with the AIDS dementia complex) not taking zidovudine were positive for HIV I p24 antigen, whereas none of 37 cerebrospinal fluid samples from patients with AIDS (two with the AIDS dementia complex) taking zidovudine were positive. CONCLUSIONS--The incidence of AIDS dementia complex in patients with AIDS declined after the introduction of systematic treatment with zidovudine; the AIDS dementia complex might be prevented by inhibiting viral replication in the central nervous system.     

Molecular and serologic analysis of IgG1 deficiency caused by new forms of the constant region of the Ig H chain gene deletions

Selective IgG1 deficiency is a rare disease. We report a familial form of IgG1 deficiency, in which IgG1 was undetectable in a 5-yr-old girl with a history of asthma and respiratory tract infections. Her father had an IgG1 level that was one-third of the mean amount found in normal healthy controls. The defect in the proband was caused by a homozygous deletion of the structural gene for C gamma 1. A Southern blot analysis demonstrated that the maternal haplotype contained a deletion encompassing C gamma 1, C psi epsilon 1, C alpha 1, C psi gamma, and C gamma 2, whereas the deletion on the paternal haplotype was confined to the C gamma 1 gene. Neither of these deletions has previously been reported. IgG1 normally constitutes the dominant isotype for antibodies directed against protein Ag, including viral proteins. We have analyzed the immune response to a number of different protein and polysaccharide Ag in the patient and her parents. In the proband, antiviral antibodies were restricted to the IgG3 and IgG4 subclasses. However, the total amount of IgG directed against several viruses was below the concentration found in normal seropositive individuals. The father and the paternal grandfather, both with low serum IgG1 levels, also had asthma, thus indicating a possible causal relationship.     

Functional and morphological identification of FSH- and LH-producing cells in the pituitary gland

The identification of pituitary FSH and LH cells in states of pharmacological treatment influencing the pituitary FSH and LH production was performed by histological staining at the isoelectric points of these hormones in the cat. The intensity of the stained material in the hormone-producing cells was determined by a microphotometric technique. As a physiological control, the FSH and LH levels in blood were measured by a radioimmunoassay.     

Rat liver microsomal progesterone metabolism: evidence for differential troleandomycin and pregnenolone 16 alpha-carbonitrile inductive effects in the cytochrome P-450 III family

The effect of Troleandomycin (TAO) and pregnenolone 16 alpha-carbonitrile (PCN) on the hepatic microsomal progesterone metabolism in the rat is evaluated. Over thirteen hydroxylated progesterone derivatives are detected, including the novel 6 beta, 21-, 6 beta, 16 alpha-, 6 beta, 16 beta- and 2,21-dihydroxy derivatives, suggesting the induction of several cytochrome P-450 isozymes. PCN treatment results overall in an augmented production of progesterone metabolites whereas TAO treatment both induces and represses specific hydroxylase activities. Progesterone metabolism with purified isozymes isolated from liver microsomes from TAO and PCN treated rats differs significantly from that observed with intact microsomes, reflecting the complexity of the induction pattern of the cytochrome P-450 III family.     

Effects of data smoothing on the reconstruction of helical axis parameters in human joint kinematics

In biomechanical joint-motion analyses, the continuous motion to be studied is often approximated by a sequence of finite displacements, and the Finite Helical Axis (FHA) or "screw axis" for each displacement is estimated from position measurements on a number of anatomical or artificial landmarks. When FHA parameters are directly determined from raw (noisy) displacement data, both the position and the direction of the FHA are ill-determined, in particular when the sequential displacement steps are small. This implies, that under certain conditions, the continuous pathways of joint motions cannot be adequately described. The purpose of the present experimental study is to investigate the applicability of smoothing (or filtering) techniques, in those cases where FHA parameters are ill-determined. Two different quintic-spline smoothing methods were used to analyze the motion data obtained with Roentgenstereophotogrammetry in two experiments. One concerning carpal motions in a wrist-joint specimen, and one relative to a kinematic laboratory model, in which the axis positions are a priori known. The smoothed and non-smoothed FHA parameter errors were compared. The influences of the number of samples and the size of the sampling interval (displacement step) were investigated, as were the effects of equidistant and nonequidistant sampling conditions and noise invariance.     

Production of 5-methoxypodophyllotoxin in cell suspension cultures of Linum flavum L.

Cell suspension cultures of Linum flavum L., routinely grown on a NAA-containing medium, accumulated low levels of the phenylpropanoid-derived lignan 5-methoxypodophyllotoxin (5-MPT), up to 0.004% on a dry weight basis. Feeding experiments with the precursor L-phenylalanine resulted in a 3–5-fold increase in 5-MPT levels, but caused the levels of PAL activity to fall. Treatment of the cultures with the elicitor Nigeran, either alone or in combination with phenylalanine, caused the 5-MPT production to cease, even though PAL activity was rapidly enhanced by these treatments. Transfer of the cultures to NAA-free medium resulted in a 40–50 fold higher level of 5-MPT accumulation, the PAL activity levels being lowered compared to the routinely grown cells. With these more differentiated cultures, phenylalanine feeding and elicitor treatment, both on its own and in combination with the precursor, had no effect on 5-MPT production, even though the PAL activity levels were higher than in the untreated cells. It can be concluded that in lignan-accumulating cultures of L. flavum, PAL activity is nearly always detectable and seems to show a reciprocal relationship with 5-MPT accumulation.Abbreviations 5-MPT 5-methoxypodophyllotoxin - PAL phenylalanine ammonia lyase (EC 4:3:1.5) - NAA naphthaleneacetic acid